巴西神经管缺陷儿童中MTHFR基因C677T和A1298C突变的代谢效应

Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects.

作者信息

Cunha Andrea L A, Hirata Mario H, Kim Chong A, Guerra-Shinohara Elvira M, Nonoyama Kymio, Hirata Rosario D C

机构信息

Department of Clinical and Toxicological Analysis of the Faculty of Pharmaceutical Sciences, University of Sao Paulo, Ave Prof. Lineu Prestes 580, B1 17, 05508-900, Brazil.

出版信息

Clin Chim Acta. 2002 Apr;318(1-2):139-43. doi: 10.1016/s0009-8981(01)00764-1.

DOI:10.1016/s0009-8981(01)00764-1

PMID:11880124

Abstract

BACKGROUND

Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations.

METHODS

The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from Sao Paulo City. Both C677T and A1298C mutations were analyzed by PCR-FLRP. The effects of MTHFR mutations on folate, vitamin B12 and homocysteine concentrations were also evaluated.

RESULTS

C677T and A1298C allele frequencies in NTDs children and mothers were similar to that found in controls. Eleven in 23 NTDs patients and 10 in 21 NTDs mothers had folate or vitamin B12 concentrations in the lower end of the normal range. In NTDs children, C677T MTHFR genotypes did not affect vitamins and homocysteine concentrations, but plasma homocysteine was higher (p=0.028) in patients with 1298AA MTHFR genotype. Moreover, 677CT/1298AA haplotype was associated with lower vitamin B12 concentrations (p<0.05) in NTDs children.

CONCLUSIONS

MTHFR gene mutations may affect vitamin B12 and homocysteine metabolism in Brazilian children with NTDs.

摘要

背景

亚甲基四氢叶酸还原酶（MTHFR）缺乏会导致叶酸代谢受损，并被认为是神经管缺陷（NTDs）的一个风险因素。在一些人群中，C677T和A1298C这两种MTHFR突变都与NTDs有关。

方法

测定了来自圣保罗市的25名患有NTDs的儿童、患儿母亲以及75名健康个体中C677T和A1298C MTHFR突变的频率。通过聚合酶链反应-荧光共振能量转移（PCR-FLRP）分析C677T和A1298C两种突变。还评估了MTHFR突变对叶酸、维生素B12和同型半胱氨酸浓度的影响。

结果

患有NTDs的儿童及其母亲中C677T和A1298C等位基因频率与对照组相似。23名NTDs患者中有11名，21名NTDs患儿母亲中有10名的叶酸或维生素B12浓度处于正常范围的下限。在患有NTDs的儿童中，C677T MTHFR基因型不影响维生素和同型半胱氨酸浓度，但1298AA MTHFR基因型的患者血浆同型半胱氨酸水平较高（p = 0.028）。此外，677CT/1298AA单倍型与患有NTDs的儿童维生素B12浓度较低有关（p < 0.05）。